Near-physiological-temperature serial crystallography reveals conformations of SARS-CoV-2 main protease active site for improved drug repurposing

DURDAĞI S., Dag C., Dogan B., Yigin M., Avsar T., Buyukdag C., ...Daha Fazla

STRUCTURE, cilt.29, sa.12, ss.1382-1403, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 29 Sayı: 12
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.str.2021.07.007
  • Dergi Adı: STRUCTURE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, BIOSIS, Chemical Abstracts Core, Communication Abstracts, EMBASE, INSPEC, MEDLINE, Metadex, Civil Engineering Abstracts
  • Sayfa Sayıları: ss.1382-1403
  • İstanbul Teknik Üniversitesi Adresli: Hayır

Özet

The COVID-19 pandemic has resulted in 198 million reported infections and more than 4 million deaths as of July 2021 (covid19.who.int). Research to identify effective therapies for COVID-19 includes: (1) designing a vaccine as future protection; (2) de novo drug discovery; and (3) identifying existing drugs to repurpose them as effective and immediate treatments. To assist in drug repurposing and design, we determine two apo structures of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease at ambient temperature by serial femtosecond X-ray crystallography. We employ detailed molecular simulations of selected known main protease inhibitors with the structures and compare binding modes and energies. The combined structural and molecular modeling studies not only reveal the dynamics of small molecules targeting the main protease but also provide invaluable opportunities for drug repurposing and structure based drug design strategies against SARS-CoV-2.